Opioid dependence is a significant public health problem. Individuals with opioid dependence exhibit frontal brain dysfunction and cognitive impairment. In addition to potentially affecting the ability to perform daily activities such as driving a car or performing complex tasks in the workplace, cognitive impairment may affect the ability to participate in and benefit from cognitive/psychosocial aspects of substance abuse treatment. Yet, few studies have attempted to remediate cognitive functions in substance abusers, and no study has specifically targeted opioid dependence. Working memory (WM) is a critical cognitive function whose core component is the 'central executive'(set of executive functions), and is a necessary building block for the performance of other cognitive functions. WM is impaired in opioid dependence and has been shown to modulate inhibitory control and decision making in substance abusers and to predict substance abuse treatment outcomes. The proposed theoretically driven cognitive training procedure (WM Training) targets working memory, and has been shown to increase working memory capacity in a variety of clinical populations (including conditions associated with frontal dysfunction) and to transfer to other cognitive domains, which is rarely observed in training studies. This innovative study will test the effects of 25 sessions of WM Training in a controlled design with 3 groups: methadone maintenance patients (MMP) who perform WM Training (MMP TRAIN), MMP who do not perform WM Training (MMP CONTROL), and healthy volunteers who perform WM Training (HV TRAIN). A battery of state-of-the art cognitive measures will be administered before and after training, and substance abuse treatment outcomes will be included as secondary outcomes. Specific Aim 1 is to test the hypothesis that MMP TRAIN will show improved performance on the trained working memory tasks at the end versus the beginning of WM Training. Specific Aim 2 is to test the hypothesis that MMP TRAIN will show significantly greater improvement in working memory and other cognitive tasks, relative to MMP CONTROL. Specific Aim 3 is to test the hypothesis that HV TRAIN will show improved working memory and cognitive performance after relative to before WM Training (as a replication within the study of previous WM Training studies). Secondary aims are to compare the magnitude of improved performance following WM Training in MMP relative to healthy volunteers without drug abuse histories, and to test whether MMP show improved substance abuse treatment outcomes following WM Training. Study findings will provide clinically relevant information about the potential of cognitive training to improve cognitive functioning in opioid dependent patients, and will enhance scientific understanding of learning capacity and the malleability of frontally based cognitive processes to training procedures in opioid dependence. In addition to the broad implications for daily functioning, definitively establishing the effects of cognitive training on cognitive functions is a necessary first step in the systematic study of training effects on substance abuse treatment outcomes. PUBLIC HEALTH RELEVANCE: Individuals with opioid dependence exhibit cognitive impairment, which may affect daily functioning and substance abuse treatment outcomes. This study will test the ability of an innovative and theoretically based cognitive training procedure to improve cognitive functioning in methadone maintenance patients.